Interactions of substance P with putative mediators of inflammation and ATP.

Substance P has recently been localized in sensory nerves and has been suggested to be the mediator of antidromic vasodilatation. Interactions of substance P with putative mediators of inflammation and adenosine 5'-triphosphate were studied in rats using a quantitative Evans blue dye-leakage technique. Rats anaesthetized with either were given Evans blue. i.v. and intracutaneous injections of inflammatory agents were given into the shaved abdominal skin. Doses of substance P, 1-5 X 10(-10) mol, produced graded dye leakage. A low dose of substance P (5 X 10(-11) mol) potentiated responses to 5-hydroxytryptamine (2.5 X 10(-10) mol), bradykinin (5 X 10(-10) mol), prostaglandin E1 (5 X 10(-10) mol) and adenosine 5'-triphosphate (2.5 X 10(-7) mol) but no histamine (2 X 10(-8) mol). A higher dose of substance P (5 X 10(-10) mol) was potentiated by prostaglandin E1 (5 X 10(-11) mol) and adenosine 5'triphosphate (5 X 10(-9) mol) but but not by histamine (5 X 10(-10) mol) or bradykinin (5 X 10(-11 mol) and was inhibited by 5-hydroxytryptamine (5 X 10(-12) mol). If substance P is released from sensory nerves in some inflammatory states these interactions might be of importance in determining the response observed.